Involvement of Prostaglandin E2 in the P2Y1 Receptor‐mediated Tonic Contraction of the Rabbit Urinary Bladder

Abstract

Previously we have provided evidence that excitatory ADP activated P2Y1 receptors contribute for the rabbit urinary bladder contractility. To determine the mechanisms involved in P2Y1-mediated signaling, we have carried out experiments with the isolated rabbit urinary bladder detrusor smooth muscle strips. The contractile responses evoked by ADP or the specific P2Y1 receptor agonist ADPβS were antagonized by the non-selective cyclooxygenase inhibitors indomethacin and meclofenamic acid, as well as by AACOCF3 (10μM), a specific inhibitor of the receptor activated cytosolic Phospholipase A2 (cPLA2). The contractile responses of the detrusor smooth muscle evoked by prostaglandin E2 (PgE2) (EC50, 0.3 μM) but not by PgF2α resembled that evoked by ADPβS (EC50, 0.6 μM). Pretreatment with SC19220 (30 μM), a selective antagonist of the EP1 subtype of the PgE2 receptors abolished contractile responses evoked by ADPβS, while AL-8810, a selective FP (PgF2α) receptor antagonist had no effect. RT-PCR experiments demonstrated that the rabbit detrusor smooth muscle expresses mRNA for the microsomal prostaglandin E2 synthase-2 (mPGES-2). This evidence suggests that activation of P2Y1 receptors may lead to the synthesis of PgE2, which acts in a paracrine manner to evoke and possible amplify the contractile response of the detrusor smooth muscle of the urinary bladder. Supported by NIH HL38126 and the Foundation for Research.